Phase I/II Study of SGI-110 With Irinotecan Versus Regorafenib or TAS-102 in Metastatic Colorectal Cancer

NCT ID: NCT01896856

Last Updated: 2020-10-06

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 118 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2013-10-23
• Study Completion Date: 2019-08-26

Brief Summary

This is a phase I/II study of the combination of Guadecitabine (SGI-110) and previously treated metastatic colorectal cancer patients. This study will be conducted in two components. First, patients will be enrolled in a phase I study of SGI-110 combined with irinotecan in a standard 3+3 design. After the maximum tolerated dose (MTD) is determined, patients will subsequently be enrolled in a 2:1 randomized phase II study of SGI-110 and irinotecan versus the standard of care regorafenib or Lonsurf (TAS-102).

Conditions

Previously Treated Metastatic Colorectal Cancer

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Phase 1: Dose Escalation

Subjects receive SGI-110 on days 1-5 and irinotecan on days 8 and 15 of each 28-day cycle.

Various doses of SGI-110 are tested to determine the maximum tolerated dose in combination with irinotecan.

Group Type: EXPERIMENTAL

SGI-110 Dose Escalation

Intervention Type: DRUG

• Dose level 1 (DL1): 45 mg/m^2 administered as a subcutaneous injection
• Dose level 1G (DL1G): 45 mg/m^2 administered as a subcutaneous injection + growth factor support
• Dose level -1 (DL-1): 30 mg/m^2 administered as a subcutaneous injection
• Dose level -1G (DL-1G): 30 mg/m^2 administered as a subcutaneous injection + growth factor support

Phase 2: Arm A SGI-110 + irinotecan

Subjects receive SGI-110 on days 1-5 and irinotecan on days 8 and 15 of each 28-day cycle.

Growth factor support (filgrastim and peg-filgrastim) is given during cycle 1 with option to give additional growth factor support at subsequent cycles per clinician judgement.

Group Type: EXPERIMENTAL

SGI-110

Intervention Type: DRUG

45 mg/m\^2 administered as a subcutaneous injection

Irinotecan

Intervention Type: DRUG

125 mg/m\^2 administered IV

Phase 2: Arm B regorafenib or TAS-102

Subjects received either regorafenib or TAS-102 based on physician and patient preference. Subjects that had received one of these standard of care drugs (regorafenib or TAS-102) prior to enrollment received the other on study.

Regorafenib taken daily from days 1-21 of each 28-day cycle or TAS-102 taken twice daily on days 1-5 and 8-12 of each 28-day cycle.

Subjects who had disease progression on Arm B were given the option to receive Arm A study drugs after a 14 day wash-out period.

Group Type: ACTIVE_COMPARATOR

Regorafenib

Intervention Type: DRUG

160 mg taken orally

TAS-102

Intervention Type: DRUG

35 mg/m\^2 taken orally

SGI-110

Intervention Type: DRUG

45 mg/m\^2 administered as a subcutaneous injection

Irinotecan

Intervention Type: DRUG

125 mg/m\^2 administered IV

Interventions

SGI-110 Dose Escalation

• Dose level 1 (DL1): 45 mg/m^2 administered as a subcutaneous injection
• Dose level 1G (DL1G): 45 mg/m^2 administered as a subcutaneous injection + growth factor support
• Dose level -1 (DL-1): 30 mg/m^2 administered as a subcutaneous injection
• Dose level -1G (DL-1G): 30 mg/m^2 administered as a subcutaneous injection + growth factor support

Intervention Type: DRUG

Regorafenib

160 mg taken orally

Intervention Type: DRUG

TAS-102

35 mg/m\^2 taken orally

Intervention Type: DRUG

SGI-110

45 mg/m\^2 administered as a subcutaneous injection

Intervention Type: DRUG

Irinotecan

125 mg/m\^2 administered IV

Intervention Type: DRUG

Other Intervention Names

Guadecitabine; Stivarga; Lonsurf; trifluridine and tipiracil; Guadecitabine; Camptosar

Eligibility Criteria

Inclusion Criteria

• Histologically or cytologically confirmed adenocarcinoma of the colon or rectum
• Phase I only: patients with biopsiable disease amenable to having two research biopsies.
• Have measurable disease
• Phase II only: progressed while receiving irinotecan therapy in the metastatic setting. There are no limitations on number of prior therapies in the metastatic setting.
• Life expectancy of greater than 12 weeks.
• Eastern Cooperative Oncology Group (ECOG) performance status <1
• Normal organ and marrow function as defined by study-specified laboratory tests
• Must use adequate contraception through the study and for 3 months after last dose of study drug.

Exclusion Criteria

• Chemotherapy or radiotherapy within 4 weeks (6 weeks for nitrosoureas or mitomycin C) of first dose of study drug or who have not recovered from treatment-related adverse events
• Receiving any other investigational agents
• Participants with known brain metastases
• History of allergic reactions attributed to compounds of similar chemical or biologic composition to irinotecan, decitabine or SGI-110.
• Received prior therapy with any hypomethylating agents.
• Uncontrolled intercurrent illness including, but not limited to ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
• Pregnant or nursing women
• History of a different malignancy are ineligible with exceptions (disease-free for at least 5 years with low risk for recurrence, cervical cancer in situ, definitively treated early stage prostate cancer, definitively treated breast ductal or lobular carcinoma in situ, and basal cell or squamous cell carcinoma of the skin).
• HIV-positive individuals on combination antiretroviral therapy
• Phase II only: previous treatment with regorafenib and TAS-102. If patients have previously received either regorafenib OR TAS-102, they must be able to receive the alternate regimen if randomized to standard of care (Arm B).
• Hospitalization for an acute medical issue within 4 weeks prior to screening visit
• Symptomatic bowel obstruction within 6 months prior to enrollment, Patients who undergo surgical correction of obstructing lesion will be eligible within 6 months.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Van Andel Research Institute

OTHER

Sponsor Role: collaborator

Astex Pharmaceuticals, Inc.

INDUSTRY

Sponsor Role: collaborator

Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Nilo Azad, MD

Role: PRINCIPAL_INVESTIGATOR

SKCCC at JHMI

Locations

USC / Norris Comprehensive Cancer Center

Los Angeles, California, United States

Sidney Kimmel Comprehensive Cancer Center

Baltimore, Maryland, United States

Memorial Sloan Kettering Cancer Center

New York, New York, United States

VU Medisch Centrum

Amsterdam, , Netherlands

Countries

United States; Netherlands

References

Lee V, Parkinson R, Zahurak M, Cope L, Cercek A, Verheul H, Gootjes E, Lenz HJ, Iqbal S, Jones P, Baylin S, Rami V, Ahuja N, El Khoueiry A, Azad NS. A phase II study of guadecitabine combined with irinotecan vs regorafenib or TAS-102 in irinotecan-refractory metastatic colorectal cancer patients. Int J Cancer. 2024 May 15;154(10):1794-1801. doi: 10.1002/ijc.34845. Epub 2024 Feb 5.

Reference Type: DERIVED

PMID: 38312102 (View on PubMed)

Sharma A, Vatapalli R, Abdelfatah E, Wyatt McMahon K, Kerner Z, A Guzzetta A, Singh J, Zahnow C, B Baylin S, Yerram S, Hu Y, Azad N, Ahuja N. Hypomethylating agents synergize with irinotecan to improve response to chemotherapy in colorectal cancer cells. PLoS One. 2017 Apr 26;12(4):e0176139. doi: 10.1371/journal.pone.0176139. eCollection 2017.

Reference Type: DERIVED

PMID: 28445481 (View on PubMed)

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

NA_00085870

Identifier Type: OTHER

Identifier Source: secondary_id

J1369

Identifier Type: -

Identifier Source: org_study_id